The central theme of this Program Project is related to how the kidney participates in the long-term regulation of arterial pressure and the mechanisms whereby alterations in the excretory ability of the kidney with resulting volume expansion and/or an elevation of arterial pressure can influence the vascular tone and structure of the systemic arterial vasculature. To achieve an understanding of arterial pressure regulation, it was necessary to conceptually and methodologically utilize a variety of basic disciplines with studies ranging from the cell to the whole animal. The Program is therefore a multi-disciplinary approach and utilizes physiological, biochemical, biophysical, pharmacological, and biomathematical techniques from the level of the cell to the whole animal to further our understanding of the function and interrelation of the complex biological systems which determine the long-term level of arterial pressure and the delivery of nutrients to the tissues in normal and hypertensive states. A quantitative approach to the design of the studies and the analysis of the biological systems provides a strong conceptual framework for the research within the Program.